Mediator Med23 Regulates Adult Hippocampal Neurogenesis
Mammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes includin...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00699/full |
| _version_ | 1818500825909035008 |
|---|---|
| author | Guo-Yan Chen Guo-Yan Chen Shuai Zhang Shuai Zhang Chong-Hui Li Cong-Cong Qi Ya-Zhou Wang Jia-Yin Chen Gang Wang Gang Wang Yu-Qiang Ding Yu-Qiang Ding Chang-Jun Su |
| author_facet | Guo-Yan Chen Guo-Yan Chen Shuai Zhang Shuai Zhang Chong-Hui Li Cong-Cong Qi Ya-Zhou Wang Jia-Yin Chen Gang Wang Gang Wang Yu-Qiang Ding Yu-Qiang Ding Chang-Jun Su |
| author_sort | Guo-Yan Chen |
| collection | DOAJ |
| description | Mammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes including adipogenesis, carcinogenesis, osteoblast differentiation, and T-cell activation. However, its potential functions in the nervous system remain unknown. We report here that Med23 is required for adult hippocampal neurogenesis in mouse. Deletion of Med23 in adult hippocampal neural stem cells (NSCs) was achieved in Nestin-CreER:Med23flox/flox mice by oral administration of tamoxifen. We found an increased number of proliferating NSCs shown by pulse BrdU-labeling and immunostaining of MCM2 and Ki67, which is possibly due to a reduction in cell cycle length, with unchanged GFAP+/Sox2+ NSCs and Tbr2+ progenitors. On the other hand, neuroblasts and immature neurons indicated by NeuroD and DCX were decreased in number in the dentate gyrus (DG) of Med23-deficient mice. In addition, these mice also displayed defective dendritic morphogenesis, as well as a deficiency in spatial and contextual fear memory. Gene ontology (GO) analysis of hippocampal NSCs revealed an enrichment in genes involved in cell proliferation, Pol II-associated transcription, Notch signaling pathway and apoptosis. These results demonstrate that Med23 plays roles in regulating adult brain neurogenesis and functions. |
| first_indexed | 2024-12-10T20:48:01Z |
| format | Article |
| id | doaj.art-367cdef4d25b4cba9b2e5282d4f682fa |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-10T20:48:01Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-367cdef4d25b4cba9b2e5282d4f682fa2022-12-22T01:34:11ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-07-01810.3389/fcell.2020.00699546076Mediator Med23 Regulates Adult Hippocampal NeurogenesisGuo-Yan Chen0Guo-Yan Chen1Shuai Zhang2Shuai Zhang3Chong-Hui Li4Cong-Cong Qi5Ya-Zhou Wang6Jia-Yin Chen7Gang Wang8Gang Wang9Yu-Qiang Ding10Yu-Qiang Ding11Chang-Jun Su12Department of Neurology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, ChinaKey Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, ChinaSchool of Life Sciences and Technology, ShanghaiTech University, Shanghai, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, and Department of Laboratory Animal Science, Fudan University, Shanghai, ChinaDepartment of Neurobiology, Institute of Neurosciences, School of Basic Medicine, Fourth Military Medical University, Xi’an, ChinaKey Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, ChinaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, ChinaSchool of Life Sciences, Fudan University, Shanghai, ChinaKey Laboratory of Arrhythmias, Ministry of Education of China, East Hospital, and Department of Anatomy and Neurobiology, Tongji University School of Medicine, Shanghai, ChinaState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, and Department of Laboratory Animal Science, Fudan University, Shanghai, ChinaDepartment of Neurology, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, ChinaMammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes including adipogenesis, carcinogenesis, osteoblast differentiation, and T-cell activation. However, its potential functions in the nervous system remain unknown. We report here that Med23 is required for adult hippocampal neurogenesis in mouse. Deletion of Med23 in adult hippocampal neural stem cells (NSCs) was achieved in Nestin-CreER:Med23flox/flox mice by oral administration of tamoxifen. We found an increased number of proliferating NSCs shown by pulse BrdU-labeling and immunostaining of MCM2 and Ki67, which is possibly due to a reduction in cell cycle length, with unchanged GFAP+/Sox2+ NSCs and Tbr2+ progenitors. On the other hand, neuroblasts and immature neurons indicated by NeuroD and DCX were decreased in number in the dentate gyrus (DG) of Med23-deficient mice. In addition, these mice also displayed defective dendritic morphogenesis, as well as a deficiency in spatial and contextual fear memory. Gene ontology (GO) analysis of hippocampal NSCs revealed an enrichment in genes involved in cell proliferation, Pol II-associated transcription, Notch signaling pathway and apoptosis. These results demonstrate that Med23 plays roles in regulating adult brain neurogenesis and functions.https://www.frontiersin.org/article/10.3389/fcell.2020.00699/fullMediator complex 23hippocampusproliferationcell cycleadult neural stem cells |
| spellingShingle | Guo-Yan Chen Guo-Yan Chen Shuai Zhang Shuai Zhang Chong-Hui Li Cong-Cong Qi Ya-Zhou Wang Jia-Yin Chen Gang Wang Gang Wang Yu-Qiang Ding Yu-Qiang Ding Chang-Jun Su Mediator Med23 Regulates Adult Hippocampal Neurogenesis Frontiers in Cell and Developmental Biology Mediator complex 23 hippocampus proliferation cell cycle adult neural stem cells |
| title | Mediator Med23 Regulates Adult Hippocampal Neurogenesis |
| title_full | Mediator Med23 Regulates Adult Hippocampal Neurogenesis |
| title_fullStr | Mediator Med23 Regulates Adult Hippocampal Neurogenesis |
| title_full_unstemmed | Mediator Med23 Regulates Adult Hippocampal Neurogenesis |
| title_short | Mediator Med23 Regulates Adult Hippocampal Neurogenesis |
| title_sort | mediator med23 regulates adult hippocampal neurogenesis |
| topic | Mediator complex 23 hippocampus proliferation cell cycle adult neural stem cells |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00699/full |
| work_keys_str_mv | AT guoyanchen mediatormed23regulatesadulthippocampalneurogenesis AT guoyanchen mediatormed23regulatesadulthippocampalneurogenesis AT shuaizhang mediatormed23regulatesadulthippocampalneurogenesis AT shuaizhang mediatormed23regulatesadulthippocampalneurogenesis AT chonghuili mediatormed23regulatesadulthippocampalneurogenesis AT congcongqi mediatormed23regulatesadulthippocampalneurogenesis AT yazhouwang mediatormed23regulatesadulthippocampalneurogenesis AT jiayinchen mediatormed23regulatesadulthippocampalneurogenesis AT gangwang mediatormed23regulatesadulthippocampalneurogenesis AT gangwang mediatormed23regulatesadulthippocampalneurogenesis AT yuqiangding mediatormed23regulatesadulthippocampalneurogenesis AT yuqiangding mediatormed23regulatesadulthippocampalneurogenesis AT changjunsu mediatormed23regulatesadulthippocampalneurogenesis |